Current understanding of coronary artery calcification

Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major ad-verse cardiovascular events. There are two recognized type of CAC—intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcifi-cation is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven-tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD patients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.     

Myocardial ‘no-reflow’ — Diagnosis,pathophysiology and treatment

In acute ST-segment elevation myocardial infarction (STEMI), improvement in reperfusion strategies has contributed to improvement in mortality. Nonetheless up to 40–50% of patients who achieve satisfactory epicardial patency do not necessarily achieve patency at the coronary microvascular level, a condition referred to as the ‘no-reflow’ phenomenon. The ‘no-reflow’ phenomenon is associated with a worse prognosis at follow up. The pathogenic mechanisms underlying the ‘no-reflow’ phenomenon is complex and dynamic. This includes a variable combination of mechanisms including distal atherothrombotic embolisation, ischaemic injury, reperfusion injury and heightened susceptibility of coronary microcirculation to injury. Accurate detection of ‘no-reflow’ is crucial because it is independently associated with adverse ventricular remodelling and patient prognosis. The diagnosis of ‘no-reflow’ can be made using angiography, electrocardiography, nuclear scintigraphy, myocardial contrast echocardiography or cardiovascular magnetic resonance (CMR). Despite our improved understanding on the pathogenesis and diagnosis of ‘no-reflow’, the treatment of ‘no-reflow’ remains the ‘Achilles heel’ in the treatment of patients with acute myocardial infarction. Several therapeutic strategies have been tested for the prevention and treatment of ‘no-reflow’, however none have been associated with improvement in clinical outcomes. Therefore there exists a need for ‘in-lab’ tools that will be able to aid early identification of patients at increased risk of ‘no-reflow’. This may enable patients at heightened risk of ‘no-reflow’ to be treated with the most appropriate individualised treatment early. We review the pathogenic mechanisms and diagnostic techniques of the ‘no-reflow’ phenomenon as well as the prevention and treatment strategies of the candidate mechanisms.     

Oxidative stress and ischaemia-reperfusion injury in the heart

The participation of reactive oxygen species in different cardiovascular pathologic conditions is widely recognised. One of these situations is the Ischaemia-reperfusion phenomenon where the role of oxygen free radicals (OFR) has been of particular interest. Ischaemia-reperfusion is a common phenomenon in the clinical setting and is observed in thrombolytic therapy, percutaneous transluminal coronary angioplasty (PTCA) and open-heart surgery. Several experimental and clinical studies strongly suggest that antioxidants may ameliorate reperfusion injury during open-heart surgery. In this regard, the following substances have been used: mannitol, deferoxamine, vitamin E, allopurinol and coenzyme Q₁₀. In PTCA procedures, the presence of an oxidative stress after reperfusion was also shown by several authors, but up to now, only probucol demonstrated efficacy in reducing restenosis after these techniques.     

The thrombus laden coronary artery--forget the fancy stuff, just aspirate it!

"No-reflow" is an important complication of percutaneous coronary intervention (PCI) in the setting of acute myocardial infarction and is associated with worse outcomes. Visible thrombus on the angiogram is a significant risk factor for "no-reflow". A variety of strategies have been employed to prevent this phenomenon including intracoronary vasodilators and distal protection systems. Randomized trials have not revealed any superiority of distal protection devices despite the theoretical rationale to their use. We describe a case of a thrombus-laden right coronary artery in which PCI would have likely resulted in significant "no-reflow". A simple aspiration catheter was used to significantly reduce the thrombus burden. Subsequent stenting was performed with no adverse events. This case illustrates the benefit of a less fancy approach to the thrombus-filled coronary artery - just aspirate it! Randomized trials are needed to test the role of simple aspiration prior to stenting in thrombus-laden coronary arteries.     

Pulmonary edema following conversion of tachyarrhythmia. A case following burst atrial pacing

Restoration of normal sinus rhythm is usually followed by improved hemodynamics. By contrast, pulmonary edema and cardiovascular collapse have been reported following successful electrical reversion of various tachyarrhythmias to normal sinus rhythm. The mechanism for this adverse reaction is not clear but has been thought to relate, at least in part, to electrical myocardial damage from the countershock. This report describes a patient in whom this complication occurred on two occasions, first following external countershock and subsequently following burst atrial pacing. Thus, conversion to sinus rhythm may be responsible for this phenomenon independent of the method of conversion.     

Assessing Coronary Flow Physiology with Intracoronary Doppler Following Coronary Interventions

Although coronary angiography has been the gold standard for assessing coronary artery stenoses, it yields information primarily about the anatomical severity of coronary artery disease, which frequently does not correlate with its physiological severity. Coronary interventions (PTCA, atherectomy, laser, etc.) are performed primarily to improve coronary flow physiology. Coronary flow physiology may be a more important end point than angiography following coronary interventions that were performed to normalize coronary flow physiology. In addition, the physiological significance of angiographically intermediate stenoses should he assessed before proceeding with catheter-based revascularization. Currently, the Doppler guidewire is available for routine clinical assessment of coronary flow physiology in the Cardiac Catheterization Lab. Several Doppler measurements have been used to assess the physiological effect of a stenosis, including the diastolic-systolic velocity ratio, proximal-distal velocity ratio, coronary flow reserve, continuity equation, and the hyperemic diastolic pressure-flow relationship. The Doppler derived coronary flow reserve correlates highly with stress nuclear perfusion images. These Doppler measurements have been made following PTCA, directional atherectomy, rotational atherectomy, and excimer laser. Following coronary interventions, adverse clinical events may be predicted if there is impaired flow physiology or cyclic flow variations. Many of the Doppler measurements used for assessing the lesion severity remain abnormal following successful coronary interventions for reasons unrelated to the lesion. Conversely, normalization of coronary physiology does not guarantee an adequate anatomical result. Further clinical trials will provide a more complete definition of the exact role for coronary flow velocity assessment following coronary interventions. (J Interven Cardiol 1996;9:163–173)     

Anemia and blood transfusion: Prognostic implications in patients undergoing contemporary percutaneous coronary intervention

Several studies have shown a direct relationship between anemia and adverse outcomes in the general patient population undergoing surgical cardiac and noncardiac procedures and in patients with heart failure and acute coronary syndromes. More recently, anemia has emerged as an important independent risk factor for adverse acute and long-term outcomes in patients undergoing contemporary percutaneous coronary intervention (PCI). Complicating the relationship between anemia and adverse outcomes following PCI is the recent identification of a possible further adverse relationship between blood transfusion and clinical outcomes. Modification of procedure strategies aimed at reducing blood losses, and the application of available guidelines for blood transfusion could be used as potential strategies for reducing the number and frequency of transfusions and improving outcomes in anemic patients undergoing PCI.     

Tako-Tsubo-Kardiomyopathie – eine neue kardiale Entität?

In recent years, a new cardiac syndrome with transient left ventricular dysfunction has been widely reported in Japan. This new entity has been referred to as "tako-tsubo cardiomyopathy" or "apical ballooning", named for the particular shape of the end-systolic left ventricle in ventriculography. This syndrome has also been reported to occur in the western population. The clinical characteristics of this phenomenon have been described as follows: (1) acute onset of reversible left ventricular apical wall motion abnormalities (ballooning) with chest pain, (2) electrocardiographic changes (i.e., ST elevation), (3) minimal myocardial enzymatic release, and (4) no significant stenosis on coronary angiography. Severe emotional or physical stress usually precedes this cardiomyopathy. A unifying mechanistic explanation responsible for this acute but rapidly reversible contractile dysfunction is still lacking. Several investigations suggested catecholamine-mediated cardiotoxicity or coronary artery vasospasm, microvascular injury, an impaired fatty acid metabolism, or transient obstruction of the left ventricular outflow. The optimal treatment of patients presenting with this syndrome may depend on the stage of condition, since various pathophysiological mechanisms underlie the final clinical picture.     

Restenosis following coronary angioplasty

Restenosis is the most important problem limiting the success of coronary angioplasty. Clinically, restenosis is seen in approximately one-third of patients undergoing percutaneous transluminal coronary angioplasty. Several clinical and angiographic risk factors have been identified which may contribute to the development of restenosis. Histopathologic studies indicate that restenosis is characterized by intimal proliferation of smooth muscle cells in a loose connective tissue matrix. These intimal lesions are associated predominantly with the nonatheromatous portion of the vessel wall. Thinning of the media of the plaque-free wall and marked fragmentation of the internal elastic lamina are also seen. Traumatic injury of the vessel wall during angioplasty probably triggers a series of cellular and subcellular events which may ultimately lead to myointimal proliferation and restenosis. Although the exact mechanism by which this occurs is unknown, several factors may enhance smooth muscle cell growth and therefore may play a role in the development of restenosis. These include platelet deposition, mechanical stretching of the media, inflammation of the vessel wall, the activity of growth factors, and alterations in vessel geometry. These possible mechanisms of restenosis suggest several potential ways to limit the proliferative response to vascular injury. Anticoagulants and platelet antagonists, direct inhibitors of smooth muscle proliferation, anti-inflammatory agents, growth factor inhibitors, and new devices which improve final vessel geometry are currently being tested as methods to curb restenosis. Unfortunately, no treatment has yet been shown to reduce significantly the rate of restenosis following angioplasty. The problem of restenosis will most likely be solved by better understanding of the basic molecular and biologic phenomena involved in vascular injury and repair.     

Homocysteine and coronary risk

Hyperhomocysteinemia has recently emerged as a potentially major risk factor in the pathogenesis of coronary artery disease. Various genetic and nongenetic factors influence plasma homocysteine status. The mechanism associating hyperhomocysteinemia with atherosclerosis, if any, is still unclear, but homocysteine may have an adverse effect on vascular endothelium. Folic acid in low doses may ameliorate this process. Several studies are examining the influence of homocysteine-lowering therapy with folic acid on the risk of atherosclerotic vascular disease.     

心肌缺血再灌注损伤机制研究的回顾与展望

心肌梗死是全球冠心病患者死亡的主要原因之一。在急性心肌梗死早期行经皮冠状动脉介入术、冠状动脉旁路移植术、药物等治疗手段,可恢复缺血区心肌组织血供,挽救濒死的心肌,降低患者的致死率。然而,心肌血供中断后,一定时间内再通恢复血供后,原缺血心肌可发生较缺血时更为严重的损伤,这一现象称为心肌缺血再灌注损伤(MIRI),其发生机制尚未完全阐明。文章就近年来MIRI机制的研究进展作一综述,阐述MIRI的病理生理机制,将有助于开发新的治疗干预手段,为临床治疗心肌梗死提供帮助。     

Pathobiology and Clinical Impact of Reperfusion Injury

Reperfusion injury refers to cellular death or dysfunction caused by restoration of blood flow to previously alchemic tissue. This should be differentiated from the normal reparative processes that follow an ischemic insult. Four types of reperfusion injury have been described in the literature: (1) lethal reperfusion injury, (2) nonlethal reperfusion injury, (myocardial stunning), (3) reperfusion arrhythmias, and (4) vascular injury (including the "no-reflow" phenomenon). There is continued debate whether reperfusion itself is capable of killing viable myocytes, which otherwise would have survived the ischemic insult. However, there is firm evidence for the existence of myocardial stunning following various ischemic syndromes, including reperfusion therapy for acute myocardial infarction, unstable angina pectoris, vasospastic angina, effort-induced ischemia, coronary artery bypass surgery, and cardiac transplantation. Reperfusion arrhythmia is more common after short ischemic episodes than after long ischemic periods. Thus, while reperfusion arrhythmias in the setting of acute myocardial infarction are relatively rare, reperfusion arrhythmias may be an important cause of sudden death. The "no-reflow" phenomenon has been described following reperfusion in patients with acute myocardial infarction. Three major components have been proposed as mediators of reperfusion injury: (1) oxygen free radicals, (2) the complement system, and (3) neutrophils. Numerous experimental studies have shown short-term benefit by blocking various stages of the postischemic inflammatory response. Oxygen free radicals scavengers, complement inhibition, leukocyte depletion, and the use of antibodies against various adhesion molecules have shown a reduction of infarct size in many ischemic/reperfusion experimental models. However, many of these agents failed to show a benefit in the clinical setting. Moreover, the long-term benefit of such intervention is still unknown.     

Myocardial ischemia-reperfusion injury and the influence of inflammation

Acute myocardial infarction is caused by a sudden coronary artery occlusion and leads to ischemia in the corresponding myocardial territory which generally results in myocardial necrosis. Without restoration of coronary perfusion, myocardial scar formation will cause adverse remodelling of the myocardium and heart failure. Successful introduction of percutaneous coronary intervention and surgical coronary artery bypass grafting made it possible to achieve early revascularisation/reperfusion, hence limiting the ischemic zone of myocardium. However, reperfusion by itself paradoxically triggers an exacerbated and accelerated injury in the myocardium, called ischemia-reperfusion (I/R) injury. This mechanism is partially driven by inflammation through multiple interacting pathways. In this review we summarize the current insights in mechanisms of I/R injury and the influence of altered inflammation. Multiple pharmacological and interventional therapeutic strategies (ischemic conditioning) have proven to be beneficial during I/R in preclinical models but were notoriously unsuccessful upon clinical translation. In this review we focus on common mechanisms of I/R injury, altered inflammation and potential therapeutic strategies. We hypothesize that a dual approach may be of value because I/R injury patients are predestined with multiple comorbidities and systemic low-grade inflammation, which requires targeted intervention before other strategies can be fully effective.     

Severe delayed thrombocytopenia associated with abciximab (ReoPro) therapy.

Acute thrombocytopenia associated with abciximab therapy has been well described, although the exact mechanism remains obscure. We report a case of delayed severe thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention that occurred following hospital discharge. The detection of this phenomenon is important as it may portend heightened risk for severe or profound thrombocytopenia on subsequent reexposure to abciximab therapy.     

Pharmacological Prevention of Peri-, and Post-Procedural Myocardial Injury in Percutaneous Coronary Intervention

In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.Key Words: Coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology.     

Histopathological findings of the no-reflow phenomenon following coronary intervention for acute coronary syndrome

Although no-reflow phenomenon may occur in patients that experience reperfusion after ischemia, there have been no reports describing the postmortem findings in these patients. We describe the findings of an autopsy in a 56-year-old man who experienced acute coronary syndrome with no-reflow phenomenon after coronary intervention. Macroscopic study demonstrated myocardial infarction with diffuse hemorrhage, and microscopic analysis revealed vascular damage and microembolization in the no-reflow area. In conclusion, coronary microembolization and damage to the small coronary artery may contribute to the pathogenesis of no-reflow phenomenon following coronary intervention in humans.     

Prognostic impact of sex on clinical outcomes following emergent coronary angioplasty in acute myocardial infarction

BACKGROUND: Several studies have shown that women had greater risk for adverse clinical outcomes following coronary angioplasty. We aimed to assess the impact of sex on clinical results following emergent coronary angioplasty in acute myocardial infarction. METHODS: We used our database of patients treated for acute myocardial infarction using emergent coronary angioplasty between January 2001 and December 2003. Procedural and angiographic results and clinical outcomes up to 6 months were collected and adjudicated for major cardiac adverse events. The outcome of 352 patients with acute myocardial infarction (71 women, 281 men, no cardiogenic shock) undergoing emergent angioplasty was analyzed and compared according to sex. RESULTS: Acute myocardial infarction occurred at an older age among women who tended to suffer more from diabetes mellitus and hypertension. In addition, on average, women had smaller culprit vessel diameters than men. The immediate post-procedural data were notable for higher frequency of 'no/slow re-flow' angiographic phenomenon in women than in men (10.5 vs. 3.4%, P=0.04). In-hospital and 30-day mortality was three times higher in women than men (women vs. men: in hospital 7 vs. 2.1%, P=0.05; 30 days 9.9 vs. 3.2%, P=0.02). At 6 months, major adverse cardiac events rate was 28 vs. 15% among women vs. men (P=0.01). Multivariate analysis showed a strong trend towards increased mortality at 30 days among women undergoing acute myocardial infarction angioplasty although it was not significantly or independently related to increased mortality (odds ratio=3.1; confidence intervals=0.8-12.5; P=0.11). CONCLUSION: Our results indicate a trend towards higher early mortality among female patients sustaining acute myocardial infarction and treated using emergent percutaneous coronary intervention that was probably because of increased age and worse coronary flow restoration results among women compared with men.     

A Mid-Ventricular Variant of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) was initially recognized in Japan in 1990. The typical patient is a postmenopausal woman with symptoms that mimic an acute coronary syndrome generally following physical or emotional stress. The EKG will typically have dynamic ST segment changes, while the angiogram will usually show normal coronary arteries. In classic TC, the left ventriculogram typically shows akinesis and ballooning of the apex with a normal or hyperdynamic base. Several variants of TC have been described. In this case report, we describe a midventricular variant of TC in a 64-year-old Hispanic female. The patient had chest pain, shortness of breath, elevated cardiac enzymes, and ST-segment elevations in leads II, aVF, and V5-V6. Coronary angiography revealed normal coronary arteries. Left ventriculogram showed hypokinesis of the midventricular segment and hyperdynamic apical and basal regions. Although the exact mechanism of TC is unknown, several theories include loss of estrogen, catecholamine or neurohumoral stimulation, coronary artery spasm, and left ventricular outflow tract (LVOT) obstruction.     

Cardiomyopathy from 1,1-Difluoroethane Inhalation

Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including “sudden sniffing death.” Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days’ nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE’s effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.     

Coronary artery dissection following radiofrequency ablation for atrial fibrillation: Case report and review of the literature

Coronary artery injury following catheter ablation for cardiac arrhythmias is very rare. We present a case of left circumflex (LCx) coronary artery dissection causing inferoposterior ST-elevation myocardial infarction following radiofrequency (RF) ablation for atrial fibrillation (AF) in a 39-year-old male with no cardiovascular risk factors. This was confirmed on coronary angiography and intracoronary vascular ultrasound (IVUS). The likely etiology is thermal injury during RF ablation for AF, due to the close proximity of the left atrial appendage and left pulmonary veins to the LCx. He was successfully treated with primary percutaneous coronary intervention with good outcome. This is, to our knowledge, the first reported case of proven acute coronary dissection secondary to RF ablation for AF reported in the literature, and highlights the importance of considering this as a mechanism for coronary occlusion in these patients.